Prefrontal modulation of anxiety through a lens of noradrenergic signaling

Frontiers in Systems Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Апрель 17, 2023

Anxiety disorders are the most common class of mental illness in U.S., affecting 40 million individuals annually. is an adaptive response to a stressful or unpredictable life event. Though evolutionarily thought aid survival, excess intensity duration anxiogenic can lead plethora adverse symptoms and cognitive dysfunction. A wealth data has implicated medial prefrontal cortex (mPFC) regulation anxiety. Norepinephrine (NE) crucial neuromodulator arousal vigilance believed be responsible for many anxiety disorders. NE synthesized locus coeruleus (LC), which sends major noradrenergic inputs mPFC. Given unique properties LC-mPFC connections heterogeneous subpopulation neurons known involved regulating anxiety-like behaviors, likely modulates PFC function cell-type circuit-specific manner. In working memory stress response, follows inverted-U model, where overly high low release associated with sub-optimal neural functioning. contrast, based on current literature review individual contributions disorders, we propose model level- adrenergic receptor-dependent, NE-PFC modulation Further, advent new techniques measure unprecedented spatial temporal resolution will significantly help us understand how

Язык: Английский

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Molecular and spatial profiling of the paraventricular nucleus of the thalamus

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 3, 2023

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked cellular differences, molecular identity spatial distribution cell types remain unclear. To address this gap, here we used single RNA sequencing (snRNA-seq) identified five molecularly distinct neuronal subtypes in mouse brain. Additionally, multiplex fluorescent situ hybridization top marker genes revealed that are organized by a combination previously unidentified gradients. Lastly, comparing our dataset with recently published single-cell atlas yielded novel insight into PVT’s connectivity cortex, including unexpected innervation auditory visual areas. This comparison also data contains largely non-overlapping transcriptomic map multiple midline thalamic nuclei. Collectively, findings uncover unknown features anatomical organization provide valuable resource for future investigations.

Язык: Английский

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Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus

Journal of Neuroscience, Год журнала: 2024, Номер 44(13), С. e1752232024 - e1752232024

Опубликована: Фев. 20, 2024

Patients with chronic pain often develop comorbid depressive symptoms, which makes the symptoms more complicated and refractory. However, underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported specific regulatory role of paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly anterior PVT (PVA) mediating depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity CFA-CDC mice. In wild-type mice, chemogenetic activation neurons was sufficient to decrease 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated immobile time tail suspension test (TST) forced swim (FST) could only be achieved by activation. Chemogenetic inhibition reversed decreased PWTs CFA mice without TST FST immobility Surprisingly, chemogenetically inhibiting failed reverse PWTs, restored rapid-onset antidepressant S-ketamine. Further behavioral tests restraint stress indicated that neuron S-ketamine independently alleviate sensory affective pain. Molecular profiling pharmacological studies revealed 5-hydroxytryptamine receptor 1D (Htr1d) pain-related engram as potential target for treating CDC. These findings identified novel CDC molecular provided insight into neuropathology under state related drug development.

Язык: Английский

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Dissociable encoding of motivated behavior by parallel thalamo-striatal projections

Current Biology, Год журнала: 2024, Номер 34(7), С. 1549 - 1560.e3

Опубликована: Март 7, 2024

The successful pursuit of goals requires the coordinated execution and termination actions that lead to positive outcomes. This process relies on motivational states are guided by internal drivers, such as hunger or fear. However, mechanisms which brain tracks shape instrumental not fully understood. paraventricular nucleus thalamus (PVT) is a midline thalamic shapes motivated behaviors via its projections accumbens (NAc)

Язык: Английский

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Restoration of a paraventricular thalamo-accumbal behavioral suppression circuit prevents reinstatement of heroin seeking

Neuron, Год журнала: 2023, Номер 112(5), С. 772 - 785.e9

Опубликована: Дек. 22, 2023

Язык: Английский

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Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons

Neuron, Год журнала: 2024, Номер 112(8), С. 1265 - 1285.e10

Опубликована: Фев. 19, 2024

Язык: Английский

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The cell-type-specific spatial organization of the anterior thalamic nuclei of the mouse brain

Cell Reports, Год журнала: 2024, Номер 43(3), С. 113842 - 113842

Опубликована: Март 1, 2024

Understanding the cell-type composition and spatial organization of brain regions is crucial for interpreting computation function. In thalamus, anterior thalamic nuclei (ATN) are involved in a wide variety functions, yet ATN remains unmapped at single-cell resolution. Combining RNA sequencing, transcriptomics, multiplexed fluorescent situ hybridization, we identify three discrete excitatory clusters that correspond to known uncover marker genes, molecular pathways, putative functions these cell types. We further illustrate graded variation along dorsomedial-ventrolateral axis all individual additionally demonstrate anteroventral nucleus exhibits spatially covarying protein products long-range inputs. Collectively, our study reveals continuous organizational principles ATN, which will help guide interpret experiments on

Язык: Английский

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Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of the thalamus

Cell Reports, Год журнала: 2023, Номер 42(10), С. 113309 - 113309

Опубликована: Окт. 1, 2023

The paraventricular nucleus of the thalamus (PVT) projects axons to multiple areas, mediates a wide range behaviors, and exhibits regional heterogeneity in both functions axonal projections. Still, questions regarding cell types present PVT extent their differences remain inadequately addressed. We applied single-cell RNA sequencing depict transcriptomic characteristics mouse neurons. found that one most significant variances transcriptome corresponded anterior-posterior axis. While classified neurons into five types, our histological analyses showed continuity among types. discovered anterior posterior subpopulations had nearly non-overlapping projection patterns, while another population intermediate patterns. In addition, these responded differently appetite-related neuropeptides, with activation showing opposing effects on food consumption. Our studies unveiled contrasts underpin function.

Язык: Английский

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Deciphering Consciousness: The Role of Corticothalamocortical Interactions in General Anesthesia

Pharmacological Research, Год журнала: 2025, Номер 212, С. 107593 - 107593

Опубликована: Янв. 8, 2025

General anesthesia is administered to millions of individuals each year, however, the precise mechanism by which it induces unconsciousness remains unclear. While some theories suggest that shares similarities with natural sleep, targeting sleep-promoting areas and inhibiting arousal nuclei, recent research indicates a more complex process. Emerging evidence highlights critical role corticothalamocortical circuits, are involved in higher cognitive functions, controlling states modulating transitions between different conscious during anesthesia. The administration general anesthetics disrupts connectivity within these resulting reversible state unconsciousness. This review elucidates how impair interactions, thereby affecting flow information across various cortical layers disrupting higher-order functions while preserving basic sensory processing. Additionally, prefrontal cortex regulating through both top-down bottom-up pathways was examined. These findings highlight intricate interplay subcortical networks maintaining restoring consciousness under anesthesia, offering potential therapeutic targets for enhancing management.

Язык: Английский

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The encoding of interoceptive-based predictions by the paraventricular nucleus of the thalamus D2+ neurons

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Understanding how the brain integrates internal physiological states with external sensory cues to guide behavior is a fundamental question in neuroscience. This process relies on interoceptive predictions-internal models that anticipate changes body's state based inputs and prior experiences. Despite recent advances identifying neural substrates of predictions, precise neuronal circuits involved remain elusive. In our study, we demonstrate Dopamine 2 Receptor (D2+) expressing neurons paraventricular nucleus thalamus (PVT) play key roles interoception predictions. Specifically, these are engaged behaviors leading physiologically relevant outcomes, their activity highly dependent mice expected outcome. Furthermore, show chronic inhibition PVT D2+ impairs long-term performance interoceptive-guided motivated behavior. Collectively, findings provide insights into role learning updating state-dependent by integrating past experiences current conditions optimize goal-directed

Язык: Английский

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